Tolinapant (ASTX660)

Catalog No.S8681 Batch:S868101

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Technical Data

Formula

C30H42FN5O3
Molecular Weight 539.68 CAS No. 1799328-86-1
Solubility (25°C)* In vitro DMSO 100 mg/mL (185.29 mM)
Ethanol 100 mg/mL (185.29 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5% DMSO 95% Corn oil
0.625mg/ml Taking the 1 mL working solution as an example, add 50 μL of 12.5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Tolinapant (ASTX660) is a potent, non-peptidomimetic antagonist of cIAP1/2 and XIAP that inhibits the interactions between a SMAC-derived peptide and the BIR3 domains of XIAP (BIR3-XIAP) and cIAP1 (BIR3-cIAP1) with IC50 values less than 40 and 12 nmol/L, respectively.
Targets
cIAP2 [1] cIAP1 [1]
(Cell-free assay)		 XIAP [1]
(Cell-free assay)
12 nM 40 nM
In vitro

ASTX660 induces proteasomal degradation of cIAP1 and 2, resulting in downstream effects of NIK stabilization and activation of noncanonical NF-kB signaling, demonstrating cIAP1/2 antagonism. Because of their roles in the evasion of apoptosis, inhibitor of apoptosis proteins (IAP) are considered attractive targets for anticancer therapy. Treatment with ASTX660 leads to TNFa-dependent induction of apoptosis in various cancer cell lines in vitro.[1]
In vivo

ASTX660 is orally bioavailable in mice and demonstrates prolonged antagonism of XIAP and cIAP1 in vivo. ASTX660 dosing in mice bearing breast and melanoma tumor xenografts causes growth inhibition of MDA-MB-231 and A375 xenograft tumors in vivo.[1]

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    MDA-MB-231, HEK293, A375, SK-MEL-28, WSU-DLCL2

  • Concentrations

    1 nM - 10 μM

  • Incubation Time

    5 min - 4 h

  • Method

    Live cell imaging. Cells are incubated with ASTX660 in 0.1% (v/v) DMSO, with or without neutralizing anti-TNFa antibody for 5 days, and live images are taken every 3 hours using a 10× objective.
Animal Study:

[1]
  • Animal Models

    male BALB/c wild type mice, male SCID mice with MDA-MB-231 xenografts, male nude mice with A375 xenografts

  • Dosages

    5, 10, 20 mg/kg

  • Administration

    Oral gavage

Selleck's Tolinapant (ASTX660) has been cited by 5 publications

EGFR inhibits TNF-α-mediated pathway by phosphorylating TNFR1 at tyrosine 360 and 401 [ Cell Death Differ, 2024, 31(10):1318-1332] PubMed: 38789573
EGFR inhibits TNF-α-mediated pathway by phosphorylating TNFR1 at tyrosine 360 and 401 [ Cell Death Differ, 2024, 10.1038/s41418-024-01316-3] PubMed: 38789573
Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer [ Heliyon, 2023, 9(10):e20655] PubMed: 37867861
Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer [ Heliyon, 2023, 9(10):e20655] PubMed: 37867861
Novel smac mimetic ASTX660 (Tolinapant) and TNF-α synergistically induce necroptosis in bladder cancer cells in vitro upon apoptosis inhibition [ Biochem Biophys Res Commun, 2022, 602:8-14] PubMed: 35247703

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.